Adolfo Díez-Pérez

Consorci MAR Parc de Salut de Barcelona, Barcino, Catalonia, Spain

Are you Adolfo Díez-Pérez?

Claim your profile

Publications (201)817.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. Methods This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. Results The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. Discussion Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. Conclusions Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.
    No preview · Article · Jan 2016 · Aging - Clinical and Experimental Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reference point indentation is a novel method to assess bone material strength index (BMSi) in vivo. We found that BMSi at the mid-tibia was weakly associated with spine and hip areal bone mineral density but not with prevalent fracture in a population-based cohort of 211 older women. Introduction Reference point indentation is a novel method to assess BMSi in vivo. Lower BMSi has been observed in patients with prior fracture than in controls, but no association between BMSi and areal bone mineral density (aBMD) has been found. Population-based association studies and prospective studies with BMSi and fractures are lacking. We hypothesized that BMSi would be associated with prevalent fractures in older Swedish women. The aim was to investigate the associations between BMSi, aBMD, and prevalent fracture in older women. Methods Two hundred eleven women, mean age 78.3 ± 1.1 years, were included in this cross-sectional, population-based study. BMSi was assessed using the OsteoProbe device at the mid-tibia. Areal BMD of the hip, spine, and non-dominant radius was measured using dual-energy X-ray absorptiometry (DXA). Fracture history was retrieved using questionnaires, and vertebral fractures were identified using vertebral fracture assessment (VFA) by DXA. Results One hundred ninety-eight previous fractures in 109 subjects were reported. A total of 106 women had a vertebral fracture, of which 58 women had moderate or severe fractures. An inverse correlation between BMSi and weight (r = −0.14, p = 0.04) was seen, and BMSi differed according to operator (ANOVA p < 0.01). Adjusting for weight and operator in a linear regression model, we found that BMSi was positively associated with aBMD of the total hip (β = 0.14, p = 0.04), non-dominant radius (β = 0.17, p = 0.02), and lumbar spine (L1–L4) (β = 0.14, p < 0.05). Using logistic regression, we could not find any association in crude or adjusted BMSi (for age, weight, height, walking speed, calcium intake, smoking, bisphosphonate and glucocorticoid use, and operator) with prevalent fractures. Conclusion We conclude that BMSi is associated with aBMD but not with prevalent fracture in a population-based cohort of 211 older women.
    No preview · Article · Dec 2015 · Osteoporosis International
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. Methods: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). Results: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. Conclusions: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy.
    Preview · Article · Dec 2015 · BMC Medical Genomics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: It is unclear what the impact of obesity has on the progression of knee osteoarthritis (KOA), from diagnosis to knee replacement (KR) surgery. This research examines the relative risk of KR surgery in overweight/obese patients with newly diagnosed knee osteoarthritis in a community population. Methods: Subjects were selected from the SIDIAP database, which compiles comprehensive clinical information collected by healthcare professionals for 80% of the population of Catalonia, Spain (>5.5 million people). Patients newly diagnosed with KOA in primary care between 2006 and 2011 were included. KR was ascertained using ICD-9-CM codes from linked hospital admissions data. Multivariable Cox regression models were fitted for KR according to BMI, and were adjusted for relevant confounders. Population proportional attributable risk was calculated. Results: 105,189 participants were followed up for a median (inter-quartile range) of 2.6 (1.3-4.2) years. 7,512 (7.1%) patients underwent KR. Adjusted HRs for KR were: 1.41 (95% CI 1.27 to 1.57) for overweight, 1.97 (1.78 to 2.18) for obese I, 2.39 (2.15 to 2.67) for obese II, and 2.67 (2.34 to 3.04) for obese III compared to normal-weight. The effect of BMI on risk of KR was stronger amongst younger participants. The population attributable risk of obesity for KOA-related KR is 31.0%. Conclusion: Overweight and obese patients are at over 40% and 100% increased risk of KR surgery compared to normal-weight respectively. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for KR surgery by 31% amongst KOA patients. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Arthritis and Rheumatology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low <5%; intermediate ≥5% and <7.5%; high ≥7.5%) taken from a prospective cohort "FRIDEX". Methods: A retrospective study of 1090 women aged ≥40 and ≤90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed. Results: When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group. Conclusions: Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.
    Full-text · Article · Nov 2015 · Maturitas
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. Methods: This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods. Results: In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. Conclusions: Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.
    Full-text · Article · Sep 2015 · Maturitas
  • [Show abstract] [Hide abstract]
    ABSTRACT: The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies.
    No preview · Article · Aug 2015 · Calcified Tissue International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although a number of reports suggest very low persistence with oral bisphosphonates, there is limited data on persistence with other anti-osteoporosis medications. We compare rates of early discontinuation (in the first year) with all available outpatient anti-osteoporosis drugs in Catalonia, Spain. We conducted a population-based retrospective cohort study using data from the SIDIAP database. SIDIAP contains computerized primary care records and pharmacy dispensing data for >80 % of the population of Catalonia (>5 million people). All SIDIAP participants starting an anti-osteoporosis drug between 1/1/2007 and 30/06/2011 (with 2 years wash-out) were included. We modelled persistence as the time between first prescription and therapy discontinuation (refill gap of at least 6 months) using Fine and Gray survival models with competing risk for death. We identified 127,722 patients who started any anti-osteoporosis drug in the study period. The most commonly prescribed drug was weekly alendronate (N = 55,399). 1-Year persistence ranges from 40 % with monthly risedronate to 7.7 % with daily risedronate, and discontinuation was very common [from 49.5 % (monthly risedronate) to 84.4 % (daily risedronate)] as was also switching in the first year of therapy [from 2.8 % (weekly alendronate) to 10 % (daily alendronate)]. Multivariable-adjusted models showed that only monthly risedronate had better one-year persistence than weekly alendronate and teriparatide equivalent, whilst all other therapies had worse persistence. Early discontinuation with available anti-osteoporosis oral drugs is very common. Monthly risedronate, weekly alendronate, and daily teriparatide are the drugs with the best persistence, whilst daily oral drugs have 40-60 % higher first-year discontinuation rates compared to weekly alendronate.
    No preview · Article · Jul 2015 · Calcified Tissue International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of ≥2 fractures while on treatment (≥2 FWOT) among users with high adherence. Fractures were considered after six months from treatment initiation and up to six months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) (Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001 respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p-exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ≥2 FWOT among patients having persisted with treatment ≥6months with overall medication possession ratio (MPR) ≥80%. Incidence of ≥2 FWOT was 2.4 (95% Confidence Interval (CI): 1.8-3.2) and 1.7 (95% CI: 1.2-2.2) per 1000 Person Years (PYs) within Catalonia and Denmark respectively. Older age was predictive of ≥2FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR) = 2.28 (95% CI: 1.11-4.68) and SHR = 2.61 (95% CI: 0.98-6.95) respectively for 65 to <80 years and SHR = 3.19 (95% CI: 1.33-7.69) and SHR = 4.88 (95% CI: 1.74-13.7) respectively for ≥80 years. Further significant predictors of ≥2 FWOT identified within only one cohort were dementia, SHR = 4.46 (95% CI: 1.02-19.4) (SIDIAP) and history of recent or older fracture, SHR = 3.40 (95% CI: 1.50-7.68) and SHR = 2.08 (95% CI: 1.04-4.15) respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain multiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent/old fracture and dementia within one but not both populations. Additional and/or alternative strategies should be investigated for these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the B-ABLE cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (p<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of aromatase inhibitor-induced bone loss.
    No preview · Article · Jun 2015 · Journal of Molecular Endocrinology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background We previously reported that 1 year of treatment with the sclerostin antibody romosozumab (Romo) was associated with increased bone mineral density (BMD) and bone formation and with decreased bone resorption in postmenopausal women with low BMD.1 Here, we report the results of 2 years of treatment with Romo, followed by 1 year of denosumab (DMAb) or placebo. Methods This phase 2 study enrolled 419 postmenopausal women age 55 to 85 years with a lumbar spine, total hip, or femoral neck T-score ≤ –2.0 and ≥ –3.5. For the results described here, women received 1 of 5 regimens of Romo (70 mg QM, 140 mg QM, 210 mg QM, 140 mg Q3M, 210 mg Q3M; data for the 210 mg QM group are shown in the figure) or placebo for 2 years. At the end of 2 years, eligible women entered a 1-year extension phase and were re-randomized 1:1 within their original treatment group to placebo or DMAb 60 mg Q6M. Only women who entered the extension were included in these analyses. Results Romo led to rapid and marked increases in lumbar spine and total hip BMD during year 1 and continued increases through year 2. The largest gains were observed with Romo 210 mg QM, with BMD increases of 15.7% (lumbar spine) and 6.0% (total hip) (Figure). Women receiving Romo 210 mg QM who transitioned to DMAb continued to accrue BMD at a rate similar to that in the second year of Romo; in those who transitioned to placebo, BMD returned toward pretreatment levels. Romo induced rapid stimulation of bone formation (P1NP) and decreased bone resorption (CTX). Increases in P1NP were transitory, returning toward baseline within 6 to 12 months and remaining below baseline through year 2. CTX remained below baseline through year 2. In women receiving Romo 210 mg QM who transitioned to DMAb, P1NP and CTX decreased; in those who transitioned to placebo, P1NP gradually returned to pretreatment levels, while CTX initially increased above baseline and gradually returned toward baseline. Adverse events were balanced between the placebo and Romo groups during the first 2 years of the study (with the exception of injection site reactions, most reported as mild) and in the placebo and DMAb groups during year 3. Conclusions Romo led to rapid and marked increases in lumbar spine and total hip BMD over 2 years, which continued with DMAb and resolved after transition to placebo. These data suggest that the treatment effects observed with Romo are further augmented by follow-on treatments like DMAb. References Disclosure of Interest M. McClung Grant/research support from: Amgen, Merck, Consultant for: Amgen, Lilly, Merck, A. Chines Shareholder of: Amgen, Employee of: Amgen, J. Brown Grant/research support from: Actavis, Amgen, Eli Lilly, Merck, Novartis, Consultant for: Amgen, Eli Lilly, Speakers bureau: Amgen, Eli Lilly, A. Diez-Perez Shareholder of: Active Life Scientific, Grant/research support from: Amgen, Consultant for: Amgen, Eli Lilly, Speakers bureau: Amgen, Eli Lilly, GSK, Novartis, ViiV, H. Resch: None declared, J. Caminis Shareholder of: UCB, Employee of: UCB, M. Bolognese Grant/research support from: Amgen, Regeneron, Eli Lilly, Speakers bureau: Amgen, S. Goemaere: None declared, H. Bone Grant/research support from: Amgen, Merck, Novartis, NPS, Consultant for: Amgen, Merck, Novartis, Tarsa, J. Zanchetta Grant/research support from: Amgen, MSD, Radius, Consultant for: Amgen, Eli Lilly, MSD, GSK, J. Maddox Shareholder of: Amgen, Employee of: Amgen, O. Rosen Shareholder of: Amgen, Employee of: Amgen, S. Bray Shareholder of: Amgen, Employee of: Amgen, A. Grauer Shareholder of: Amgen, Employee of: Amgen
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the association between socio-economic status (SES) and risk of hand, hip or knee osteoarthritis at a population level. Retrospective ecological study using the SIDIAP database (primary care anonymized records for > 5 million people in Catalonia (Spain)). Urban residents > 15 years old (2009-2012) were eligible. Validated area-based SES deprivation index MEDEA (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) was estimated for each area based on census data as well as incident diagnoses (ICD-10 codes) of hand, hip or knee osteoarthritis (2009-2012). Zero-inflated Poisson models were fitted to study the association between MEDEA quintiles and the outcomes. Compared to the least deprived, the most deprived areas were younger (43.29 (17.59) versus 46.83 (18.49), years (Mean SD), had fewer women (49.1% versus 54.8 %), a higher percentage of obese (16.2 % versus 8.4 %), smokers (16.9 % versus 11.9%) and high-risk alcohol consumption subjects (1.5% versus 1.3 %). Compared to the least deprived, the most deprived areas had an excess risk of osteoarthritis: age-sex-adjusted IRR 1.26 (1.11-1.42) for hand, 1.23 (1.17-1.29) hip, and 1.51 (1.45-1.57) knee. Adjustment for obesity attenuated this association: 1.06 (0.93 -1.20), 1.04 (0.99-1.09), and 1.23 (1.19-1.28) respectively. Deprived areas have higher rates osteoarthritis (hand, hip, knee). Their increased prevalence of obesity accounts for a 50% of the excess risk of knee osteoarthritis observed. Public health interventions to reduce the prevalence of obesity in this population could reduce health inequalities. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Mar 2015 · Osteoarthritis and Cartilage
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tenofovir is involved in accelerated bone mineral density (BMD) loss. We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables. Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P < 0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples. The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Mar 2015 · Journal of Antimicrobial Chemotherapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment-induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation, technique could detect bone tissue properties changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca + D) supplements or anti-osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring Bone Material Strength index (BMSi). Bone mineral density was measured by dual-energy x-ray absorptiometry (DXA). While Ca + D-treated patients exhibited substantial and significant deterioration, risedronate-treated patients exhibited no significant change, and both denosumab- and teriparatide-treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared to baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation following treatment with osteoporosis therapies in patients newly exposed to glucocorticoids. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Mar 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
  • Ankita Modi · Jackson Tang · Shuvayu Sen · Adolfo Díez-Pérez
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: In clinical trials, bisphosphonate therapy reduces but does not eliminate the risk of fracture. The objective of this retrospective observational study was to examine fracture rates among women who were adherent to bisphosphonate therapy for at least 1 year. Methods: We studied outcomes for women ≥50 years old who received their first osteoporosis therapy as an oral bisphosphonate during 2002-2008 and were enrolled in a large claims database for ≥3 consecutive years, including a baseline year before and 2 years after the index prescription (thus, the full study period was 2001-2010). Adherence during the first year of therapy was defined as a medication possession ratio (MPR) ≥80% (total number of days' supply/365 days × 100%). Results: Of the 62,446 women who met the eligibility criteria, 26,852 (43%) had an MPR ≥80% for osteoporosis therapy during year 1. In year 2, the fracture rate was 52/1000 patient-years. Fragility fractures were recorded for 1292 patients (4.8%) during the baseline year (before initiating therapy); for 1051 patients (3.9%) during year 1 (adherence year); and for 871 patients (3.2%) during year 2. Significant predictors of fracture in year 2 were older age, higher comorbidity score, comorbid inflammatory joint disease, and prior fragility fracture during the baseline year or first year of treatment. The primary limitation of these results is the scope of the claims database, which did not provide information on bone mineral density, supplemental use of calcium or vitamin D, or reasons for initiating oral bisphosphonates. Conclusions: Despite being adherent to bisphosphonate treatment for 1 year, 3.2% of women experienced a fracture in the subsequent year. These results suggest an unmet need in patients with osteoporosis and an opportunity for newer therapies to help address this need.
    No preview · Article · Feb 2015 · Current Medical Research and Opinion
  • [Show abstract] [Hide abstract]
    ABSTRACT: Many studies have shown a correlation between chronic kidney disease (CKD) and fracture. However, an increased mortality in CKD patients is a competing risk scenario, not accounted for in previously. Our aim was to investigate the true impact of CKD on hip fracture after accounting for a competing risk with death. We conducted a population-based cohort study to determine the impact of CKD on hip fractures in individuals aged ≥50years old registered in SIDIAP(Q) database (representative 1.9 million people in Catalonia, Spain). Cox regression was used to estimate Hazard Ratio (HR) for death and hip fracture according to CKD status. A competing risk (Fine and Gray) model was fitted to estimate sub-HR for hip fracture in CKD or CKD-free patients accounting for differential mortality. 873,073 (32,934 (3.8%) CKD) patients were observed for 3years. 4,823 (14.6%) CKD and 36,328 (4.3%) CKD-free participants died during follow-up (HR 1.83 [95%CI 1.78-1.89]), whilst 522 (1.59%) and 6,292 (0.75%) sustained a hip fracture respectively. Adjusted Cox models showed a significantly increased risk of hip fractures for CKD group (HR 1.16 [1.06-1.27]), but this association was attenuated in competing risk models accounting for mortality (SHR 1.14 [1.03-1.27]). Both death and hip fracture rates are increased (by 83% and 16% respectively) in CKD patients. However, the association between CKD and hip fractures is attenuated when an excess mortality is taken into account. A competing risk with death must be considered in future analyses of association between CKD and any health outcomes. Copyright © 2014. Published by Elsevier Inc.
    No preview · Article · Dec 2014 · Bone
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the association between socio-economic deprivation (SES) and hip fracture risk. Retrospective cohort study using a population-based database (primary care records) of over 5 million people. Eligibility: all living subjects registered during the period 2009-2012 and resident in an urban area. Measures: a validated SES composite index (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) estimated for each area based on census data. Outcome: incident hip fracture rates as coded in medical records using ICD-10 codes. Statistics: zero-inflated Poisson models fitted to study the association between SES quintiles and hip fracture risk, adjusted for age, sex, obesity, smoking and alcohol consumption. Compared to the most deprived, wealthy areas had a higher hip fracture incidence (age-sex adjusted incidence 38.57 (37.14-40.00) compared to 34.33 (32.90-35.76) per 10,000 person-years). Similarly, most deprived areas had a crude and age-sex adjusted lower risk of hip fracture, RR of 0.71 (0.65-0.78) and RR of 0.90 (0.85-0.95) respectively compared to wealthiest areas. The association was attenuated and no longer significant after adjustment for obesity: RR 0.96 (0.90-1.01). Further adjustment for smoking and high alcohol consumption did not make a difference. Wealthiest areas have an almost 30% increased risk of hip fracture compared to the most deprived. Differences in age-sex composition and a higher prevalence of obesity in deprived areas could explain this higher risk. Copyright © 2014. Published by Elsevier Inc.
    No preview · Article · Dec 2014 · Bone
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context. Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. Objective. To improve model discrimination by developing a 5-yr composite fracture prediction model for fracture sites that display similar risk profiles. Design. Prospective, observational cohort study. Setting. Primary care practices in 10 countries. Patients. Women aged ≥55 years. Intervention. Self-administered questionnaires collected data on patient characteristics, fracture risk factors and previous fractures. Main Outcome Measure. Main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. Results. Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index 0.75, 47,066 women), and lowest for FRAX major fracture and a 10-site model (c indices 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 yr of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 yr of age from a 10% decrease to a 60% increase. Conclusions. After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
    No preview · Article · Dec 2014 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary There is scarce data on the association between early stages of type 2 diabetes and fracture risk. We report a 20 % excess risk of hip fracture in the first years following disease onset compared to matched non-diabetic patients. Introduction Type 2 diabetes mellitus (T2DM) is a chronic disease that affects several target organs. Data on the association between T2DM and osteoporotic fractures is controversial. We estimated risk of hip fracture in newly diagnosed T2DM patients, compared to matched non-diabetic peers. Methods We conducted a population-based parallel cohort study using data from the Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) database. Participants were all newly diagnosed T2DM patients registered in SIDIAP in 2006–2011 (T2DM cohort). Up to two diabetes-free controls were matched to each T2DM participant on age, gender, and primary care practice. Main outcome was incident hip fracture in 2006–2011, ascertained using the tenth edition of the International Classification of Diseases (ICD-10) codes. We used Fine and Gray survival modelling to estimate risk of hip fracture according to T2DM status, accounting for competing risk of death. Multivariate models were adjusted for body mass index, previous fracture, and use of oral corticosteroids. Results During the study period (median follow-up 2.63 years), 444/58,483 diabetic patients sustained a hip fracture (incidence rate 2.7/1,000 person-years) compared to 776/113,448 matched controls (2.4/1,000). This is equivalent to an unadjusted (age- and gender-matched) subhazard ratio (SHR) 1.11 [0.99–1.24], and adjusted SHR 1.20 [1.06–1.35]. The adjusted SHR for major osteoporotic and any osteoporotic fractures were 0.95 [0.89–1.01] and 0.97 [0.92–1.02]. Conclusions Newly diagnosed T2DM patients are at a 20 % increased risk of hip fracture even in early stages of disease, but no for all fractures. More data is needed on the causes for an increased fracture risk in T2DM patients as well as on the predictors of osteoporotic fractures among these patients.
    No preview · Article · Dec 2014 · Osteoporosis International
  • Source
    Raquel Soriano · Sabina Herrera · Xavier Nogués · Adolfo Diez-Perez
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoporosis is commonly associated with menopause and ageing. It can, however, also be caused by diseases, lifestyle, genetic diseases, drug therapies and other therapeutic interventions. In cases of secondary osteoporosis, a common rule is the management of the underlying condition. Healthy habits and calcium and vitamin D supplementation are also generally advised. In cases of high risk of fracture, specific antiosteoporosis medications should be prescribed. For most conditions, the available evidence is limited. Special attention should be paid to possible contraindications of drugs used for the treatment of postmenopausal or senile osteoporosis. Bisphosphonates are the most widely used drugs in secondary osteoporosis, and denosumab or teriparatide have been also assessed in some cases. Important research is needed to develop more tailored strategies, specific to the peculiarities of the different types of secondary osteoporosis.
    Full-text · Article · Dec 2014 · Best Practice & Research: Clinical Endocrinology & Metabolism

Publication Stats

4k Citations
817.46 Total Impact Points

Institutions

  • 2014-2015
    • Consorci MAR Parc de Salut de Barcelona
      Barcino, Catalonia, Spain
  • 2010-2015
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2009-2015
    • IMIM Hospital del Mar Medical Research Institute
      Barcino, Catalonia, Spain
  • 1998-2015
    • Autonomous University of Barcelona
      • Department of Medicine
      Cerdanyola del Vallès, Catalonia, Spain
  • 2001-2014
    • Parc de Salut Mar
      Barcino, Catalonia, Spain
  • 2000-2012
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2007-2008
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2006
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Eli Lilly
      Indianapolis, Indiana, United States